Gamma-glutamyltranspeptidase (GGT) is a cell surface associated enzyme found in cells having secretory or absorptive functions. Enhanced production of GGT and/or a dramatic increase in GGT activity can be a hallmark for detecting preneoplastic lesions of the oral cavity. The expression and regulation of GGT activity during normal and neoplastic development is important in developing an understanding of the synthetic events occurring during normal and abnormal growth. Recently, pilocarpine administration was shown to cause a significant drop in GGT activity in the acinar cells of the submandibular gland. From this report was suggested that the inhibitory effect of pilocarpine was mediated by directly affecting the enzyme. We believe the interpretation of the data by the authors of that report is in error. Since pilocarpine is known to mediate its other effects by stimulation of cholinergic receptors, we think the observed inhibition could be explained by the loss of GGT-rich membrane fragments or GGT inactivation during secretion and membrane recycling. We propose to investigate this by studying the effect of pilocarpine: on GGT activity in a non-target organ (kidney); on a purified GGT enzyme preparation and homogenate (enzyme kinetics); on another surface associated enzyme (alkaline phosphatase). Furthermore, we will directly observe GGT and GGT activity in control and pilocarpine-treated tissue by histochemical and immunohistochemical techniques. Parallel ultrastructural studies will be undertaken to improve the resolution of the above techniques.